Dehalogenation of 5-halopyrimidines by cysteine was considered to be the only reaction until Wataya et al. demonstrated that 5-bromodeoxyuridine not only undergoes dehalogenation but also forms simultaneously 5-cysteinyl deoxyuridine on treatment with cysteine. We have shown on the other hand that 5-chlorodeoxyuridine forms exclusively and quantitatively 5-cysteinyldeoxyuridine on treatment with cysteine without undergoing any detectable dehalogenation to form deoxyuridine. We propose to extend these studies to cover 5-halodeoxycytidines. 5-Iodo- and 5-bromodeoxycytidines have been found to undergo quantitative dehalogenaiton to deoxycytidine on treatment with cysteine. On the other hand, 5-chlorodeoxycytidine does not undergo dehalogenation under similar treatment. It forms two products - one containing cysteine and one without cysteine. Our objective is to identify these two products. The reaction of l-methyl-5-chlorocytosine with cysteine will also be studied to help achieve this goal by delineating the involvement of the sugar moiety in this reaction. The chemical reactivity of 5-halopyrimidines towards cellular nucleophiles like cysteine will be an indicator of its probable residence time in vivo in DNA. We have found that 5-chlorouracil is incorporated heavily in mouse liver and testes DNA when the animals ingest the base in the drinking water and 5-chlorodeoxyuridine is five times more potent than its 5-bromoanalog in inducing sister chromatid exchange in Chinase hamster ovary cells. We plan to study the incorporation of the base in mouse liver RNA and the dynamics of its possible elimination from the liver DNA after its withdrawal from their diet. The incorporation of the base in aquatic biota, e.g., blood worms (chironomid), will be studied. Possible inhibition of 5-chlorodeoxyuridine induced sister chromatid exchange by 2-deoxycytidine will be studied to shed light on the mechanism of mutagenesis by base analog substitution.